Statnick M, Dailey J, Jobe P, Browning R
Department of Physiology, Southern Illinois University, Carbondale 62901, USA.
Eur J Pharmacol. 1996 Mar 28;299(1-3):93-102. doi: 10.1016/0014-2999(95)00839-x.
Previous studies have shown that widespread depletion of brain 5-hydroxytryptamine (5-HT, serotonin) exacerbates audiogenic seizures in genetically epilepsy-prone rats (GEPRs), while elevations in brain 5-HT attenuate these seizures. However, the location of the central nervous system site(s) at which 5-HT exerts its anticonvulsant action on audiogenic seizures, remains unknown. The substantia nigra has been shown to exert modulatory actions over both brainstem and forebrain driven seizures in normal rats, and receives a rich serotonergic innervation. The present study was designed to determine if 5-HT exerts its modulatory effect on audiogenic seizures by an action in the substantia nigra. Microinfusion of 5,7-dihydroxytryptamine (4 micrograms/0.25 microliter bilateral) into the substantia nigra of GEPRs which display a moderate seizure (GEPR-3s) failed to alter the audiogenic seizure. Consistent with these findings, microinfusions of fluoxetine-HCl into the substantia nigra of severe seizure GEPRs (GEPR-9s) failed to alter any aspect of the audiogenic seizure. This effect was observed when fluoxetine was infused alone, or in combination with systemic administration of 5-hydroxytryptophan (75 mg/kg, i.p.). The present findings argue against a modulatory role of nigral 5-HT on audiogenic seizures in GEPRs.
先前的研究表明，在遗传性癫痫易感大鼠（GEPRs）中，脑内5-羟色胺（5-HT，血清素）的广泛耗竭会加剧听源性癫痫发作，而脑内5-HT水平升高则会减轻这些发作。然而，5-HT对听源性癫痫发作发挥抗惊厥作用的中枢神经系统部位仍不清楚。在正常大鼠中，黑质已被证明对脑干和前脑驱动的癫痫发作均有调节作用，并且接受丰富的5-羟色胺能神经支配。本研究旨在确定5-HT是否通过作用于黑质对听源性癫痫发作发挥调节作用。向表现为中度癫痫发作的GEPRs（GEPR-3s）的黑质中微量注射5,7-二羟基色胺（4微克/0.25微升，双侧）未能改变听源性癫痫发作。与这些发现一致，向严重癫痫发作的GEPRs（GEPR-9s）的黑质中微量注射盐酸氟西汀未能改变听源性癫痫发作的任何方面。当单独注射氟西汀或与全身注射5-羟色氨酸（75毫克/千克，腹腔注射）联合使用时，均观察到了这种效果。目前的研究结果表明，黑质5-HT对GEPRs的听源性癫痫发作没有调节作用。
